1-15301347-C-T

Variant names:

• chr1-15301347-C-T
• rs757209918
• NM_001391957.1:c.821C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001391957.1(FHAD1):​c.821C>T​(p.Ser274Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000357 in 1,399,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: FHAD1 NM_001391957.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.624

Genes affected

FHAD1 (HGNC:29408): (forkhead associated phosphopeptide binding domain 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09978062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHAD1	NM_001391957.1	c.821C>T	p.Ser274Phe	missense_variant	Exon 6 of 34	ENST00000688493.1	NP_001378886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FHAD1	ENST00000688493.1	c.821C>T	p.Ser274Phe	missense_variant	Exon 6 of 34		NM_001391957.1	ENSP00000509124.1
FHAD1	ENST00000683790.1	c.821C>T	p.Ser274Phe	missense_variant	Exon 6 of 34			ENSP00000506973.1
FHAD1	ENST00000358897.8	c.821C>T	p.Ser274Phe	missense_variant	Exon 6 of 31	5		ENSP00000351770.4
FHAD1	ENST00000375998.8	c.821C>T	p.Ser274Phe	missense_variant	Exon 5 of 30	5		ENSP00000365166.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000128 AC: 2 AN: 156650 Hom.: 0 AF XY: 0.0000120 AC XY: 1 AN XY: 83000

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000917

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000165

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000357 AC: 5 AN: 1399428 Hom.: 0 Cov.: 31 AF XY: 0.00000580 AC XY: 4 AN XY: 690222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000371

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.000117 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.821C>T (p.S274F) alteration is located in exon 6 (coding exon 5) of the FHAD1 gene. This alteration results from a C to T substitution at nucleotide position 821, causing the serine (S) at amino acid position 274 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0078	T;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.55	T;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.080
Sift	Benign	0.056	T;T
Sift4G	Uncertain	0.034	D;D
Polyphen		0.21	B;B
Vest4		0.17
MVP		0.088
ClinPred		0.14	T
GERP RS		4.4
Varity_R		0.070
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs757209918; hg19: chr1-15627843;